Several studies have shown that the pulmonary toxin, paraquat, produces a marked decrease in lung NADPH without a concomitant increase in NADP+. These results suggest that paraquat either inhibits the synthesis of the pyridine dinucleotide or enhances its degradation. To investigate the possible mechanism and consequences of these observations, studies were undertaken to: 1) examine the direct interaction of paraquat with NADPH, 2) study the effect of paraquat on NAD/NADP synthesis and 3) determine if paraquat increases pyridine dinucleotide degradation by enhanced synthesis of poly ADP-ribose. Paraquat interaction with several pyridine dinucleotides was investigated after both chemical and enzymatic reduction of the substrates. Reaction products were analyzed by high pressure liquid chromatography. The interaction of paraquat with pyridine dinucleotide was also studied in rat liver and lung microsomes, lung 9000 g supernatant and after intraperitoneal injection of several doses in vivo. Chemically-reduced paraquat forms at least two distinct products in the presence of NADPH or NADH. This reaction was sensitive to the presence of oxygen. In both rat liver and lung subcellular fractions, no interaction between paraquat and the pyridine dinucleotides was apparent under either aerobic or anaerobic conditions. Presently, the possible formation of similar products from paraquat in vivo is being investigated. Subsequent experiments will quantify the effects of paraquat on the synthesis and degradation (e.g., formation of poly ADP-ribose) of NAD+ and NADP+ in order to determine if such mechanisms may account, in part, for the depletion of pulmonary nucleotides following paraquat administration.